bims-mesote 2023-07-02 papers

Issue of 2023–07–02
five papers selected by
Laura Mannarino, Humanitas Research

Curr Oncol. 2023 05 23. 30(6): 5195-5200

Multi-Institutional Patterns of Use of Tumor-Treating Fields for Patients with Malignant Pleural Mesothelioma.

Tugce Kutuk, Joshua M Walker, Matthew T Ballo, Robert B Cameron, Jean Bustamante Alvarez, Sheema Chawla, Eric Luk, Deepti Behl, Alan Dal Pra, Neil Morganstein, Tamer Refaat, Arshin Sheybani, Christian Squillante, Jun Zhang, Rupesh Kotecha.

(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6-649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9-21.6 h), representing 50% (range: 8-90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1-17 h), representing 38% (range: 13-71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.

Keywords: malignant pleural mesothelioma; real-world experience; tumor-treating fields (TTFields); usage

DOI: https://doi.org/10.3390/curroncol30060394

Clin Case Rep. 2023 Jun;11(6): e7610

A rare presentation of malignant mesothelioma of the tunica vaginalis managed with immunotherapy and review of the literature.

Kritika Mishra, Shihab Siddiquee, Anna Rachelle Mislang.

Key Clinical Message: We describe the first case in literature of malignant mesothelioma of the tunica vaginalis that has shown partial response to systemic immunotherapy (ipilimumab-nivolumab) post orchiectomy, warranting further investigation in a trial setting.
Abstract: We present a case report of an 80-year-old ex-smoker with a rare diagnosis of metastatic mesothelioma of the tunica vaginalis, managed with immunotherapy. The patient, with no known history of asbestos exposure, presented with a left scrotal mass and pain. Scrotal ultrasound confirmed a large paratesticular mass, and computed tomography (CT) of the chest, abdomen, and pelvis revealed a bilobed mass in the left scrotal compartment without associated inguinal or abdominopelvic lymphadenopathy, and an indeterminate, subcentimeter, bi-basal subpleural nodules. He underwent a left orchiectomy, and histopathology confirmed the diagnosis of a paratesticular mesothelioma. Postoperatively, the patient had a positron emission tomography (PET) scan showing a new right pleural effusion as well as increasing size of the lobar and pleural nodules bilaterally, all metabolically active and suggestive of progressive metastatic disease. The patient was commenced on ipilimumab and nivolumab immunotherapy, a regimen indicated for malignant pleural mesothelioma; however, the efficacy on paratesticular mesothelioma is not known. After 6 months of treatment, the patient demonstrated a partial response to immunotherapy, with a reduction in the size of known pleural nodules and effusion.Literature review suggests that diagnosis requires a high index of suspicion and patients commonly have metastatic disease at the time of diagnosis. Orchiectomy is a common management modality. However, the role, regimen, and benefits of systemic therapy are unclear, warranting further studies investigating management strategies.

Keywords: genomic profiling; orchiectomy; systemic immunotherapy; testicular mesothelioma

DOI: https://doi.org/10.1002/ccr3.7610

J Thorac Oncol. 2023 Jun 23. pii: S1556-0864(23)00632-9. [Epub ahead of print]

European Epidemiology of Pleural Mesothelioma - Real-life data from a joint analysis of the Mesoscape database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma database.

ETOP Mesoscape and ESTS consortia

INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy with increasing prevalence and poor prognosis. Real-life data are a unique approach to reflect the reality of PM epidemiology, treatment, and prognosis in Europe.
PATIENTS AND METHODS: A joint analysis of the European Thoracic Oncology Platform (ETOP) Mesoscape and the European Society of Thoracic Surgeons (ESTS) databases was performed to better understand the characteristics and epidemiology of PM, including histology, staging, and treatment. Overall survival (OS) was assessed, adjusting for parameters of clinical interest.
RESULTS: The analysis included 2766 patients (Mesoscape:497/10 centers / ESTS:2269/77 centers). The primary histology was epithelioid (71%), with 57% stage III-IV patients. Within Mesoscape, patients received either multimodality (59%) or palliative intention treatment (41%). The median follow-up was 47.2 months, based on 1103 patients (Mesoscape:491/ESTS:612) with 823 deaths and median OS 17.4 months. In multivariable analysis, female gender, epithelioid subtype, and lower stage were associated with longer OS, when stratifying by cohort, age, and ECOG PS. Within Mesoscape, multimodality treatment including surgery was predictive of longer OS (HR=0.56 (95%CI:0.45-0.69)), adjusting for gender, histologic subtype, and ECOG PS. Overall, surgical candidates with a macroscopic complete resection (MCR) had a significantly longer median OS compared to patients with R2 (25.2m vs 16.4m; log-rank p<0.001).
CONCLUSION: This combined ETOP/ESTS database analysis offers one of the largest databases with detailed clinical and pathological outcome. Our finding reflects a benefit for selected patients that undergo multimodality treatment, including MCR, and represents a valuable resource to inform the epidemiology and treatment options for individual patients.

Keywords: MCR; epidemiology; multimodality treatment; pleural mesothelioma; real-world data; registry

DOI: https://doi.org/10.1016/j.jtho.2023.06.011

Br J Cancer. 2023 Jun 27.

SETDB1 tumour suppressor roles in near-haploid mesothelioma involve TP53.

Mengting Xu, Yuqing Tu, Wenhui Bi, Meijun Z Lundberg, Isabella Klooster, Jonathan A Fletcher, Wen-Bin Ou.

BACKGROUND: Mutational inactivation of the SETDB1 histone methyltransferase is found in a subset of mesothelioma, particularly in cases with near-haploidy and TP53 mutations. However, the tumourigenic consequences of SETDB1 inactivation are poorly understood.
METHODS: In this study, we investigated SETDB1 tumour suppressor functions in mesothelioma and explored biologic relationships between SETDB1 and TP53.
RESULTS: Immunoblotting of early passage cultures showed that SETDB1 was undetectable in 7 of 8 near-haploid mesotheliomas whereas SETDB1 expression was retained in each of 13 near-diploid mesotheliomas. TP53 aberrations were present in 5 of 8 near-haploid mesotheliomas compared to 2 of 13 near-diploid mesotheliomas, and BAP1 inactivation was demonstrated only in near-diploid mesotheliomas, indicating that near-haploid and near-diploid mesothelioma have distinct molecular and biologic profiles. Lentiviral SETDB1 restoration in near-haploid mesotheliomas (MESO257 and MESO542) reduced cell viability, colony formation, reactive oxygen species levels, proliferative marker cyclin A expression, and inhibited growth of MESO542 xenografts. The combination of SETDB1 restoration with pemetrexed and/or cisplatin treatment additively inhibited tumour growth in vitro and in vivo. Furthermore, SETDB1 restoration upregulated TP53 expression in MESO542 and MESO257, whereas SETDB1 knockdown inhibited mutant TP53 expression in JMN1B near-haploid mesothelioma cells. Likewise, TP53 knockdown inhibited SETDB1 expression. Similarly, immunoblotting evaluations of ten near-diploid mesothelioma biopsies and analysis of TCGA expression profiles showed that SETDB1 expression levels paralleled TP53 expression.
CONCLUSION: These findings demonstrate that SETDB1 inactivation in near-haploid mesothelioma is generally associated with complete loss of SETDB1 protein expression and dysregulates TP53 expression. Targeting SETDB1 pathways could be an effective therapeutic strategy in these often untreatable tumours.

DOI: https://doi.org/10.1038/s41416-023-02330-x

Indian J Surg Oncol. 2023 Jun;14(Suppl 1): 30-38

Rare Variants of Malignant Peritoneal Mesothelioma: a Literature Review.

Ambarish Chatterjee, Aditi Bhatt.

Primary peritoneal mesothelioma (PM) is a rare and aggressive malignancy that arises from the peritoneum and classified into diffuse malignant peritoneum mesothelioma (DMPM) and borderline variants, viz. multicystic peritoneal mesothelioma (MCPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM). The borderline variants are rarer than conventional DMPM, are less aggressive form accounting for 3-5% of all cases of peritoneal mesothelioma. In this narrative review article, we have discussed the pathogenesis, clinical presentation, natural history, and management of these rarer variants of PM, viz. MCPM and WDPPM. Histologically, MCPM typically consists of small cysts composed of mesothelial epithelium with benign bland cuboidal cells with clear fluids; cells lack cellular atypia and have increased number of mitoses. WDPPM has specific papillary component with myxoid plump cores and single layer of bland mesothelial cells. Both the variants commonly present as incidental finding or symptoms of chronic abdominal pain, chronic pelvic inflammatory disease, pelvic mass, and infertility. In the absence of treatment, these diseases are slow growing with major concerns being that both the variants have malignant transformation capabilities and a high rate of recurrence. In the light of current evidences, it is recommended that MCPM and WDPPM patients should be offered a complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy consisting of cisplatin and doxorubicin. Collaborative multi-institutional studies are needed to generate more data and formulate robust guidelines.

Keywords: Cytoreductive surgery; HIPEC; Malignant mesothelioma; Multicystic peritoneal mesothelioma; Well-differentiated papillary mesothelioma

DOI: https://doi.org/10.1007/s13193-023-01754-4